title: Leucine supplementation protects from insulin resistance by regulating adiposity levels.
abstract: BACKGROUND
  Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed.
  
  
  RESULTS
  Male C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed.
  
  
  CONCLUSIONS
  These findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation is lacking in already obese animals, a phenomenon possibly related to the extent of the obesity before starting the supplementation.
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, Bordeaux, France ; Université de Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, Bordeaux, France.
authors.forename: Elke
authors.initials: E
authors.lastname: Binder
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Bermúdez-Silva
authors.forename: Caroline
authors.initials: C
authors.lastname: André
authors.forename: Melissa
authors.initials: M
authors.lastname: Elie
authors.forename: Silvana Y
authors.initials: SY
authors.lastname: Romero-Zerbo
authors.forename: Thierry
authors.initials: T
authors.lastname: Leste-Lasserre
authors.forename: Ilaria
authors.initials: I
authors.lastname: Belluomo
authors.forename: Adeline
authors.initials: A
authors.lastname: Duchampt
authors.forename: Samantha
authors.initials: S
authors.lastname: Clark
authors.forename: Agnes
authors.initials: A
authors.lastname: Aubert
authors.forename: Marco
authors.initials: M
authors.lastname: Mezzullo
authors.forename: Flaminia
authors.initials: F
authors.lastname: Fanelli
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
authors.forename: Daniela
authors.initials: D
authors.lastname: Cota
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D059305:Diet, High-Fat; D019587:Dietary Supplements; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D007930:Leucine / Q000097:blood / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010084:Oxidation-Reduction / Q000187:drug effects; D010641:Phenotype; D015430:Weight Gain / Q000187:drug effects
chemical_list: D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D007930:Leucine; D005947:Glucose